Recently, the pathogenesis of schizophrenia has been suggested to involve dysfunction of dopamine D1 receptors in the medial prefrontal cortex (mPFC). Which is resulted in dopamine D2 receptor hyperactivity in subcortical regions such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc). D1 receptors dysfunction is involved in the negative symptoms of schizophrenia whereas the D2 receptors hyperactivity results in the positive symptoms of this disorder. According to this new hypothesis, an effective antipsychotic drug should have both D1 receptor agonist and D2 receptor antagonist dual actions.
Tetrahydroprotoberberine analogues (THPBs) have this dual actions, including l-Stepholidine (l-SPD) and l-chloroscoulerine (ZL94112235.2, CN03151464.2). l-SPD is an active ingredient of the Chinese herb Stephania. l-CSL is a derivative of l-SPD. In preliminary clinic studies, l-SPD showed favorable activity and few side effects in the treatment of schizophrenia. So, the efficacy of THPBs for neuron system disease especially schizophrenia merits further investigation.